TY - JOUR
T1 - Fluorobenzoyllysinepentanedioic Acid Carbamates
T2 - New Scaffolds for Positron Emission Tomography (PET) Imaging of Prostate-Specific Membrane Antigen (PSMA)
AU - Yang, Xing
AU - Mease, Ronnie C.
AU - Pullambhatla, Mrudula
AU - Lisok, Ala
AU - Chen, Ying
AU - Foss, Catherine A.
AU - Wang, Yuchuan
AU - Shallal, Hassan
AU - Edelman, Hannah
AU - Hoye, Adam T.
AU - Attardo, Giorgio
AU - Nimmagadda, Sridhar
AU - Pomper, Martin G.
N1 - Publisher Copyright:
© 2015 American Chemical Society.
PY - 2016/1/14
Y1 - 2016/1/14
N2 - Radiolabeled urea-based low-molecular weight inhibitors of the prostate-specific membrane antigen (PSMA) are under intense investigation as imaging and therapeutic agents for prostate and other cancers. In an effort to provide agents with less nontarget organ uptake than the ureas, we synthesized four 18F-labeled inhibitors of PSMA based on carbamate scaffolds. 4-Bromo-2-[18F]fluorobenzoyllysineoxypentanedioic acid (OPA) carbamate [18F]23 and 4-iodo-2-[18F]fluorobenzoyllysine OPA carbamate [18F]24 in particular exhibited high target-selective uptake in PSMA+ PC3 PIP tumor xenografts, with tumor-to-kidney ratios of >1 by 4 h postinjection, an important benchmark. Because of its high tumor uptake (90% injected dose per gram of tissue at 2 h postinjection) and high tumor-to-organ ratios, [18F]23 is promising for clinical translation. Prolonged tumor-specific uptake demonstrated by [18F]24, which did not reach equilibrium during the 4 h study period, suggests carbamates as alternative scaffolds for mitigating dose to nontarget tissues.
AB - Radiolabeled urea-based low-molecular weight inhibitors of the prostate-specific membrane antigen (PSMA) are under intense investigation as imaging and therapeutic agents for prostate and other cancers. In an effort to provide agents with less nontarget organ uptake than the ureas, we synthesized four 18F-labeled inhibitors of PSMA based on carbamate scaffolds. 4-Bromo-2-[18F]fluorobenzoyllysineoxypentanedioic acid (OPA) carbamate [18F]23 and 4-iodo-2-[18F]fluorobenzoyllysine OPA carbamate [18F]24 in particular exhibited high target-selective uptake in PSMA+ PC3 PIP tumor xenografts, with tumor-to-kidney ratios of >1 by 4 h postinjection, an important benchmark. Because of its high tumor uptake (90% injected dose per gram of tissue at 2 h postinjection) and high tumor-to-organ ratios, [18F]23 is promising for clinical translation. Prolonged tumor-specific uptake demonstrated by [18F]24, which did not reach equilibrium during the 4 h study period, suggests carbamates as alternative scaffolds for mitigating dose to nontarget tissues.
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U2 - 10.1021/acs.jmedchem.5b01268
DO - 10.1021/acs.jmedchem.5b01268
M3 - Article
C2 - 26629713
AN - SCOPUS:84955083286
SN - 0022-2623
VL - 59
SP - 206
EP - 218
JO - Journal of medicinal chemistry
JF - Journal of medicinal chemistry
IS - 1
ER -